共查询到20条相似文献,搜索用时 491 毫秒
1.
The role of LPL in reducing the serum triacylglycerol concentration was investigated in rats fed a high sucrose diet containing 0.25% (w/w) ethyl-CPIB. Compared with sucrose-fed controls, drug treatment resulted in a fall in adipose tissue LPL activity and a rise in enzyme activity in thigh and heart muscle. Serum post-heparin lipoprotein lipase activity after a high dose of heparin was lower in ethyl-CPIB-treated rats than controls, but after a low dose of heparin the values were similar. The amount of LPL activator was decreased by the drug. Thus, the low serum triacylglycerol concentration observed in the ethyl-CPIB-treated rats cannot be explained by changes in functional LPL activity. The plasma triacylglycerol-lowering effect of the drug could be explained by the observed decrease in triacylglyerol output by the liver. 相似文献
2.
Muna ZA Gudbrandsen OA Wergedahl H Bohov P Skorve J Berge RK 《Biochemical pharmacology》2002,63(6):1127-1135
We have previously shown that tetradecylthioacetic acid (TTA), a sulfur containing saturated fatty acid analogue, inhibits the oxidative modification of human low-density lipoprotein (LDL) in vitro. The oxidative modification of LDL is believed to be a crucial step in the progression of atherosclerosis. In the present study, we investigated the effect of TTA oral administration on the susceptibility of rat lipoprotein to undergo oxidative modification ex vivo. Lipoprotein resistance to copper-induced oxidation was highly improved after TTA administration to rats. Conjugated dienes produced after 150 min of lipoprotein oxidation were dramatically lowered in the TTA treated rats compared to controls. Malondialdehyde and lipid peroxides production by oxidation was highly limited. These effects were independent of any Vitamin E effects. More than 50% relative reduction in polyunsaturated fatty acids of the n-3 family, and more than 30% relative increase in 18:1n-9 fatty acid in the triacylglycerol (TAG)-rich lipoprotein were observed. TAG-rich lipoprotein lipids of TTA fed rats were decreased with more than 50% reduction in TAG. The data reported in this paper indicate a potent in vivo antioxidant capability of TTA that beside its hypolipidemic effect might be of importance in relation to the development of atherosclerosis. 相似文献
3.
Very low density lipoprotein receptor (VLDLR) is a member of the low density receptor family, expressed mostly in adipose tissue, heart, and skeletal muscles. VLDLR binds apolipoprotein-E-triglyceride-rich lipoproteins and plays a key role in lipid metabolism. In adipocytes, VLDLR expression increases with differentiation but it is not known whether it plays a role in the adipogenesis. Here we report that VLDLR expression in 3T3-L1 adipocytes is upregulated by PPARγ agonist 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2) in dose- and time-dependant manners. Knockdown of peroxisome proliferator-activated receptor-γ (PPARγ) with siRNA abolished pioglitazone- and 15d-PGJ2-induced VLDLR expression and simultaneously reduced VLDL uptake in adipocytes. In addition, PPARγ-agonist treatment of control mouse adipocytes (vldlr+/+) enhanced adipogenesis and VLDL uptake concurrently with the induction of VLDLR expression. However, vldlr deficiency (vldlr−/−) significantly blunted the proadipogenic effects of PPARγ agonists. Sequence analysis revealed the presence of a putative PPARγ responsive sequence (PPRE) within the vldlr promoter, which is responsive to natural (15d-PGJ2) and synthetic (pioglitazone) PPARγ agonists. Reporter gene assays using serial deletion of the 5′-flanking region showed that this putative PPRE site induced promoter transactivation, while a site-targeted mutation abolished transactivation. Moreover, electrophoresis mobility shift assay (EMSA) and chromatic immunoprecipitation (ChIP) assays showed the specific binding of PPARγ to the PPRE sequence.Together, these results support a crucial function for VLDLR in adipocyte differentiation and mediation of the proadipogenic effect of PPARγ. 相似文献
4.
The aim of the present study was to determine the effect of 2-hydroxy 4-methoxy benzoic acid (HMBA), the active principle of Hemidesmus indicus, an indigenous Ayurvedic medicinal plant in India. We investigated the effect of HMBA on hyperlipidaemia induced by ethanol, exploring food intake, body weight, and hepatic and plasma lipids and lipoproteins. Male Wistar rats weighing 130-180 g were given ethanol (5 g kg(-1) p.o.) daily for 30 days. Subsequently, ethanol-fed rats were given HMBA intragastrically at a dose of 200 microg kg(-1) per day for 30 days. At the end of the total experimental period of 60 days, plasma concentrations of total cholesterol (CHO), triglycerides (TG), lipoproteins (LP), phospholipids (PL), free fatty acids (FFA) and lipoprotein lipase (LPL), and hepatic CHO, TG and PL were measured. Treatment of ethanol-fed rats with HMBA significantly decreased plasma CHO, TG, LP, PL and FFA and hepatic CHO, TG and PL, and increased plasma LPL concentrations compared with values in untreated ethanol-fed rats (all P<0.05). Food intake and average body weight at the end of the experimental period were significantly increased by HMBA administration. In conclusion, administration of HMBA decreased lipids and lipoprotein concentrations significantly in an animal model of ethanol-induced hyperlipidaemia. 相似文献
5.
Dong Wook Shin Sang Min Lee Min Jeong Song Tae Ryong Lee Han Kon Kim Minsoo Noh 《Biochemical pharmacology》2009,77(1):125-171
Green tea intake has been shown to confer various health benefits to patients suffering from metabolic disorders. Here, we studied the effect of several major green tea polyphenols on adipocyte differentiation in human bone marrow mesenchymal stem cells (hBM-MSCs) and compared it to the effect of representative antidiabetic drugs. (−)-Catechin was the most potent of the eight green tea polyphenols evaluated in promoting adipocyte differentiation in hBM-MSCs, and this effect was dose-dependent. (−)-Catechin increased the mRNA levels of various adipogenic markers, such as adiponectin, peroxisome proliferator-activated receptor gamma (PPARγ), FABP4, and LPL, as measured during adipocyte differentiation in hBM-MSCs. In addition, (−)-catechin upregulated the secretion of adiponectin in hBM-MSC culture. Using a reporter gene assay and a competitive ligand binding study, (−)-catechin also significantly activated PPARγ in a dose-dependent fashion; however, (+)-catechin, the enantiomer of (−)-catechin, was not effective as a PPARγ agonist, which seems to imply that the effect of (−)-catechin on PPARγ is stereospecific. In conclusion, our data suggest that (−)-catechin promotes adipocyte differentiation and increased sensitivity to insulin in part by direct activation of PPARγ, which could be at the basis of the observed pharmacological benefits of green tea intake in reducing the risk of type 2 diabetes. 相似文献
6.
某些药物对大鼠血浆和肝脏脂蛋白脂酶活性及血浆胆固醇的影响 总被引:1,自引:0,他引:1
Lipoprotein lipase (LPL) is one of the most important factors in lipoprotein metabolism. The plasma and liver LPL activities (indicaded by fatty acid release), the ratio of LPL activity to total lipase activity and theoplasma cholesterol levels in rats treated with drugs were determined so as to study the relationship between LPL and lipoprotein metabolism.Plasma LPL activity is negatively related to the total cholesterol and high density lipoprotein cholesterol levels. As the liver LPL activity, increased, the plasma LPL activity also increased. When rats were treated with insulin, phenytoin or Radix Polygonum multiflorum, the plasma and liver LPL activities and the ratio of LPL activity to total lipase activity increased, whereas the plasma total cholesterol and high density lipoprotein cholesterol levels decreased. No significant effect of phenytoin on the total cholesterol level was observed, When large doses of phenytoin were used, the plasma very low density lipoprotein and low density lipoprotein cholesterol level increased and the ratio of high density lipoprotein cholesterol to total cholesterol decreased. 相似文献
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9.
Xueqin Zhang 《Drug delivery》2017,24(2):16-21
AbstractHigh-density lipoprotein (HDL) and low-density lipoprotein (LDL), as human endogenous lipoprotein particles, have low toxicity, high selectivity, and good safety. They can avoid the recognition and clearance of human reticuloendothelial system. These synthetic lipoproteins (sLPs) have been attracted extensive attention as the nanovectors for tumor-targeted drug and gene delivery. Herein, recent advances in the field of anticancer based on these two lipid proteins and recombinant lipoproteins (rLPs) as target delivery vectors were analyzed and discussed. 相似文献
10.
《Fundamental and applied toxicology : official journal of the Society of Toxicology》1983,3(6):502-506
The mechanism by which persistent polychlorinated biphenyls (PCBs) are redistributed from maternal storage depots to developing oocytes during estrogen-dependent vitellogenesis in rainbow trout is unknown. Since PCBs have been shown to be associated with mammalian plasma lipoproteins, and since estrogens alter lipoprotein profiles in fish, the in vitro interaction of 14C-2,4,5,2′,4′,5′-hexachlorobiphenyl(6-CB) with lipoproteins was assessed in corn oil- and estradiol benzoate (EB)-pretreated sexually immature rainbow trout. Serum was collected and pooled, and aliquots were incubated with 0.04 nmoles 6-CB for 48 hours at 12°C. Lipoproteins were separated by density flotation. Radioactivity, as well as, triacylglycerol, cholesterol, phospholipid phosphorus and protein content were assessed in each fraction. 6-CB was found to be associated with all lipoprotein classes, as well as the protein-rich bottom fraction. EB administration resulted in dose-dependent alterations in lipoprotein profiles and a shift in 6-CB association from protein and lipoproteins of higher density to those of lower density. A significant positive correlation was observed between the triacylglycerol or cholesterol content of the fractions and the percentage of 6-CB which was distributed in that fraction. 相似文献
11.
Mode of action of fibrates in the regulation of triglyceride and HDL-cholesterol metabolism 总被引:4,自引:0,他引:4
Epidemiological studies have shown that hypertriglyceridemia and low HDL-cholesterol were both associated with an increased risk of coronary heart disease. Furthermore, hypertriglyceridemia is now recognized as an independent risk factor for coronary artery disease. Secondary prevention trials (e.g., LOCAT, BECAIT, BIP and DAIS) in coronary artery disease with drugs acting primarily on triglycerides (e.g., the PPAR-alpha activators bezafibrate, fenofibrate and gemfibrozil) have shown that reducing triglycerides and increasing HDL-cholesterol, without significantly affecting LDL-cholesterol, slows down coronary artery luminal narrowing. Furthermore, the VA-HIT study recently showed that gemfibrozil decreased coronary artery disease mortality in secondary prevention trials, partly by increasing HDL-cholesterol. The peroxisome proliferator-activated receptors (PPARs) (i.e., PPAR-alpha, -beta(delta) and -gamma) form a subfamily of the nuclear receptor gene family. Whereas all PPARs are, albeit to differing extents, activated by fatty acids and derivatives, PPAR-alpha binds the hypolipidemic fibrates. PPAR-alpha activation mediates changes in lipoprotein metabolism. Moreover, PPAR-alpha activators increase hepatic uptake and esterification of free fatty acids, in addition to increasing mitochondrial free fatty acid uptake and the resulting free fatty acid oxidation. The effect of fibrates on the metabolism of triglyceride-rich lipoproteins is due to a PPAR-alpha-dependent stimulation of lipoprotein lipase and of apolipoprotein (apo)A-V and to an inhibition of apoC-III expression, whereas the increase in plasma HDL-cholesterol depends partly on an overexpression of apoA-I and apoA-II. PPARs are also expressed in atherosclerotic lesions. 相似文献
12.
The purpose of the present study was to determine whether dehydroepiandrosterone (DHEA) affects de novo fatty acid synthesis, oleic acid formation, fatty acid oxidation, and very low density lipoprotein (VLDL) secretion, in relation to the accumulation of lipid containing oleic acid, in rat liver. The rates of hepatic de novo synthesis of both fatty acid and monounsaturated fatty acid, determined by incorporation of 3H from 3H(2)O into fatty acid, were increased markedly when rats were fed a diet containing 0.5% (w/w) DHEA for 14 days. The treatment of rats with DHEA also enhanced the conversion of [14C]stearic acid into oleic acid in the liver in vivo. DHEA did not suppress fatty acid degradation in the liver. Namely, mitochondrial palmitic acid oxidation in liver homogenates and isolated hepatocytes was increased approximately 1.9- and 5-fold, respectively, in DHEA-treated rats. Peroxisomal palmitic acid oxidation in isolated hepatocytes from rats treated with DHEA, however, was not significantly different from that of the control, despite the fact that peroxisomal degradation of palmitic acid in the liver homogenates was increased markedly. The rate of hepatic VLDL secretion in DHEA-treated rats was decreased markedly. These results indicate that the elevation of the hepatic fatty acid content, especially oleic acid, by DHEA feeding is due to an increase in both de novo fatty acid synthesis and the formation of oleic acid and to a decrease in the rate of hepatic VLDL secretion. Mitochondrial and peroxisomal fatty acid degradation does not appear to play a significant role in the accumulation of hepatic lipids. 相似文献
13.
Apparent Km and Vmax values for PC and PE hydrolysis were determined following exposure of HDL, LDL, and VLDL to a basic phospholipase A2 from N. nigricollis snake venom and an acidic phospholipase A2 from N. nigricollis snake venom and an acidic phospholipase A2 from N. n. atra snake venom. Both enzymes hydrolyzed the lipoprotein phospholipids approximately as fast as they hydrolyzed pure phospholipids in mixed micelles, however, the N. nigricollis enzyme, which has a much stronger anticoagulant effect than the N. n. atra enzyme, had lower apparent Vmax values. These values were highest for phospholipids in VLDL and lowest for HDL, however, the differences between the lipoproteins were relatively small with the N. nigricollis enzyme while the differences were much larger with the N. n. atra enzyme. Fractions of the two enzymes in which varying numbers of lysines were carbamylated showed much larger differences in relative rates of phospholipid hydrolysis in HDL, LDL and VLDL. Triton X-100 eliminates these differences in rates of hydrolysis. These results are discussed in terms of the differences in the organized structure of the lipoprotein classes and in the penetration ability of the phospholipases. 相似文献
14.
目的观察油酰乙醇胺(OEA)对高脂血症模型大鼠降血脂及肝脏保护作用。方法高脂饮食建立高脂血症大鼠模型,分别观察OEA(10,203,0 mg/kg)对高脂血症大鼠的血清胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、谷丙转氨酶(ALT)、肝重和肝脏系数、肝脏丙二醛(MDA)、谷胱甘肽过氧化物酶(GSH-Px)的影响。制作冰冻切片观察大鼠肝脏脂质变性程度。结果与模型组相比,OEA(20,30mg/kg)具有降血脂作用,同时降低血清ALT、肝脏脂质、肝重和肝脏系数、肝脏MDA水平,升高肝脏GSH-Px活力。结论 OEA能降低高脂血症大鼠血脂、抑制肝脏脂肪沉积,并减轻脂质过氧化物对肝脏的损伤。 相似文献
15.
Naoki Tanaka Xiuguo Zhang Eiko Sugiyama Hiroyuki Kono Takero Nakajima Eiji Tanaka Toshifumi Aoyama 《Biochemical pharmacology》2010,80(10):1601-2067
Eicosapentaenoic acid (EPA) in fish oil is known to improve hepatic steatosis. However, it remains unclear whether such action of EPA is actually caused by peroxisome proliferator-activated receptor α (PPARα) activation. To explore the contribution of PPARα to the effects of EPA itself, male wild-type and Ppara-null mice were fed a saturated fat diet for 16 weeks, and highly (>98%)-purified EPA was administered in the last 12 weeks. Furthermore, the changes caused by EPA treatment were compared to those elicited by fenofibrate (FF), a typical PPARα activator. A saturated fat diet caused macrovesicular steatosis in both genotypes. However, EPA ameliorated steatosis only in wild-type mice without PPARα activation, which was evidently different from numerous previous observations. Instead, EPA inhibited maturation of sterol-responsive element-binding protein (SREBP)-1 in the presence of PPARα through down-regulation of SREBP cleavage-activating protein and site-1 protease. Additionally, EPA suppressed fatty acid uptake and promoted hydrolysis of intrahepatic triglycerides in a PPARα-independent manner. These effects were distinct from those of fenofibrate. Although fenofibrate induced NAPDH oxidase and acyl-coenzyme A oxidase and significantly increased hepatic lipid peroxides, EPA caused PPARα-dependent induction of superoxide dismutases, probably contributing to a decrease in the lipid peroxides. These results firstly demonstrate detailed mechanisms of steatosis-ameliorating effects of EPA without PPARα activation and ensuing augmentation of hepatic oxidative stress. 相似文献
16.
The protective role of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins in streptozotocin-induced diabetic rats has been studied. A single intraperitoneal injection of streptozotocin (50 mg kg(-1)) to rats led to a significant (P < 0.05) increase in the levels of lipids (cholesterol, triglycerides, free fatty acids and phospholipids) in plasma and tissues (liver, kidney, heart and brain). The levels of low density and very low density lipoprotein (LDL and VLDL, respectively) cholesterol were increased, whereas the levels of high density lipoprotein (HDL) cholesterol were decreased significantly (P < 0.05) in plasma. The activity of 3-hydroxy 3-methylglutaryl coenzyme A (HMG CoA) reductase increased significantly (P < 0.05) in liver, kidney and heart, and the activity of lipoprotein lipase (LPL) and lecithin cholesterol acyltransferase (LCAT) decreased significantly (P < 0.05) in the plasma of diabetic rats. Streptozotocin injection also increased the levels of glycoproteins such as hexose, hexosamine, fucose and sialic acid in plasma, liver and kidney. Oral administration of rutin to streptozotocin-induced diabetic rats significantly (P < 0.05) decreased the levels of lipids in plasma and tissues. The levels of plasma HDL-cholesterol increased and the levels of LDL- and VLDL-cholesterol decreased significantly (P < 0.05). The activity of HMG CoA reductase decreased in the tissues and the activity of plasma LPL and LCAT increased significantly (P < 0.05). The levels of glycoproteins were found to be significantly (P < 0.05) decreased in plasma, liver and kidney of rutin-treated diabetic rats. Rutin administration to normal rats did not exhibit any significant (P < 0.05) changes in any of the parameters studied. In conclusion, the beneficial effect of rutin on lipids, lipoproteins, lipid metabolizing enzymes and glycoproteins could be due to its antioxidant property. 相似文献
17.
Ganesan Pushpavalli Chinnadurai VeeramaniKodukkur Viswanathan Pugalendi 《Food and chemical toxicology》2010
Chrysin is a flavonoid that exists in nature and is the major component of some traditional medicinal herbs. We investigated the hepatoprotective and antihyperlipidaemic potential of chrysin against d-galactosamine (a single intraperitoneal injection 400 mg/kg BW) induced hepatotoxicity in male albino Wistar rats. d-GalN rats exhibited an increased hepato and nephro toxicity marker activities aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase and gamma glutamyl transpeptidase and total bilirubin level while urea, uric acid and creatinine and lipid profile. It also negatively affected the serum total protein, albumin and A/G ratio. Rats treated with chrysin at different concentrations (25, 50 and 100 mg/kg BW) caused a significant improvement in serum protein level, decreased hepato and nephro toxicity markers. It also decreased the levels of very low density lipoprotein cholesterol and low density lipoprotein cholesterol while high density lipoprotein cholesterol significantly increased. It also decreased the levels of total cholesterol, phospholipids, triglycerides, free fatty acids in the plasma and tissues of liver and kidney. The effect of chrysin (25 mg/kg) is comparable with silymarin, a known hepatoprotective drug. Chrysin thus exhibits hepatoprotective and antihyperlipidaemic activity. 相似文献
18.
Takahashi K Kamijo Y Hora K Hashimoto K Higuchi M Nakajima T Ehara T Shigematsu H Gonzalez FJ Aoyama T 《Toxicology and applied pharmacology》2011,252(3):237-249
Development of a preventive strategy against tubular damage associated with proteinuria is of great importance. Recently, free fatty acid (FFA) toxicities accompanying proteinuria were found to be a main cause of tubular damage, which was aggravated by insufficiency of peroxisome proliferator-activated receptor alpha (PPARα), suggesting the benefit of PPARα activation. However, an earlier study using a murine acute tubular injury model, FFA-overload nephropathy, demonstrated that high-dose treatment of PPARα agonist (0.5% clofibrate diet) aggravated the tubular damage as a consequence of excess serum accumulation of clofibrate metabolites due to decreased kidney elimination. To induce the renoprotective effects of PPARα agonists without drug accumulation, we tried a pretreatment study using low-dose clofibrate (0.1% clofibrate diet) using the same murine model. Low-dose clofibrate pretreatment prevented acute tubular injuries without accumulation of its metabolites. The tubular protective effects appeared to be associated with the counteraction of PPARα deterioration, resulting in the decrease of FFAs influx to the kidney, maintenance of fatty acid oxidation, diminution of intracellular accumulation of undigested FFAs, and attenuation of disease developmental factors including oxidative stress, apoptosis, and NFκB activation. These effects are common to other fibrates and dependent on PPARα function. Interestingly, however, clofibrate pretreatment also exerted PPARα-independent tubular toxicities in PPARα-null mice with FFA-overload nephropathy. The favorable properties of fibrates are evident when PPARα-dependent tubular protective effects outweigh their PPARα-independent tubular toxicities. This delicate balance seems to be easily affected by the drug dose. It will be important to establish the appropriate dosage of fibrates for treatment against kidney disease and to develop a novel PPARα activator that has a steady serum concentration regardless of kidney dysfunction. 相似文献
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Alexandra Rogue Sébastien Anthérieu Aurore Vluggens Thierry Umbdenstock Nancy Claude Catherine de la Moureyre-Spire Richard J. Weaver André Guillouzo 《Toxicology and applied pharmacology》2014
Although non-alcoholic fatty liver disease (NAFLD) is currently the most common form of chronic liver disease there is no pharmacological agent approved for its treatment. Since peroxisome proliferator-activated receptors (PPARs) are closely associated with hepatic lipid metabolism, they seem to play important roles in NAFLD. However, the effects of PPAR agonists on steatosis that is a common pathology associated with NAFLD, remain largely controversial. In this study, the effects of various PPAR agonists, i.e. fenofibrate, bezafibrate, troglitazone, rosiglitazone, muraglitazar and tesaglitazar on oleic acid-induced steatotic HepaRG cells were investigated after a single 24-hour or 2-week repeat treatment. Lipid vesicles stained by Oil-Red O and triglycerides accumulation caused by oleic acid overload, were decreased, by up to 50%, while fatty acid oxidation was induced after 2-week co-treatment with PPAR agonists. The greatest effects on reduction of steatosis were obtained with the dual PPARα/γ agonist muraglitazar. Such improvement of steatosis was associated with up-regulation of genes related to fatty acid oxidation activity and down-regulation of many genes involved in lipogenesis. Moreover, modulation of expression of some nuclear receptor genes, such as FXR, LXRα and CAR, which are potent actors in the control of lipogenesis, was observed and might explain repression of de novo lipogenesis. 相似文献